Evaluation of Hypothalamo-Pituitary-Adrenocortical Function in Children by Human Corticotropin-Releasing Hormone (MCI-028) Test

Abstract

A dose of 1.5μg/kg of MCI-028, human corticotropin-releasing hormone (hCRH), was administered intravenously to 38 children with non-endocrine short stature with normal function in the hypothalamo-pituitary-adrenocortical axis and to 71 children with a disorder in the same axis. Blood levels of adrenocorticotropic hormone (ACTH) and cortisol were determined to evaluate the axis. The 95% confidence limits of peak responses of ACTH and cortisol in non-endocrine short stature were between 17.2 and 135.3pg/ml, and between 13.1 and 35.6μg/dl, respectively, and were used as standards for children.
When compared with these standards, the hormonal responses in children with various disorders in the hypothalamo-pituitary-adrenocortical axis were as follows: in two children with Cushing's syndrome caused by adrenal tumor, ACTH values were decreased and were not responsive to hCRH, while cortisol values, though within the normal limit, were not responsive; in children with primary adrenal insufficiency or congenital adrenal hyperplasia, cortisol values were decreased and not responsive, whereas ACTH values tended to be increased and ACTH response high except for 21α-hydroxylase deficiency of congenital adrenal hyperplasia. In two cases of pituitary dwarfism complicated with ACTH deficiency, both ACTH and cortisol values were decreased and poorly responsive; and in children who were receiving glucocorticoid, both ACTH and cortisol values tended to be decreased and to respond poorly to hCRH.
As for side effects, hot flushing was observed among 8.0% of the subjects after administration of hCRH. But this symptom was not severe and no other side effects of clinical importance were observed. In conclusion, this study demonstrated that the hCRH test was also safe and useful in evaluating hypothalamo-pituitary-adrenocortical function in children.